The Kilimanjaro Diabetic Programme was initiated in response to the needs of people living with diabetes (PWLD) to identify barriers to uptake of screening for diabetic retinopathy, to improve management of di...
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Τρίτη 2 Φεβρουαρίου 2016
A needs assessment of people living with diabetes and diabetic retinopathy
Research participation after terrorism: an open cohort study of survivors and parents after the 2011 Utøya attack in Norway
Reliable estimates of treatment needs after terrorism are essential to develop an effective public health response. More knowledge is required on research participation among survivors of terrorism to interpre...
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Quantification of low molecular weight selenium metabolites in human plasma after treatment with selenite in pharmacological doses by LC-ICP-MS
Abstract
The paper presents an analytical method for quantification of low molecular weight (LMW) selenium compounds in human plasma based on liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS) and post column isotope dilution-based quantification. Prior to analysis, samples were ultrafiltrated using a cut-off value of 3000 Da. The method was validated in aqueous solution as well as plasma using standards of selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), selenite, and the selenosugar Se-methylseleno-N-acetylgalactosamine (SeGal) for linearity, precision, recoveries, and limits of detection and quantitation with satisfactory results. The method was applied for analysis of a set of plasma samples from cancer patients receiving selenite treatment in a clinical trial. Three LMW selenium compounds were observed. The main compounds, SeGal and selenite were tentatively identified by retention time matching with standards in different chromatographic systems, while the third minor compound was not identified. The identity of the selenosugar was verified by ESI-MS-MS product ion scanning, while selenite was identified indirectly as the glutathione (GSH) reaction product, GS-Se-SG.
Graphical Abstract
A method for analysing plasma samples based on spin filtering and LC-ICP-MS analysis with isotope dilution quantification was developed and applied to samples from patients receiving selenite in pharmacological doses in a clinical trial
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GC-induced tethered repression need GR SUMOylation [Pharmacology]
Upon binding of a glucocorticoid (GC), the GC receptor (GR) can exert one of three transcriptional regulatory functions. We recently reported that SUMOylation of the GR at position K293 in humans (K310 in mice) within the N-terminal domain is indispensable for GC-induced evolutionary conserved inverted repeated negative GC response element...
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GC-induced direct repression needs GR SUMOylation [Pharmacology]
Unique among the nuclear receptor superfamily, the glucocorticoid (GC) receptor (GR) can exert three distinct transcriptional regulatory functions on binding of a single natural (cortisol in human and corticosterone in mice) and synthetic [e.g., dexamethasone (Dex)] hormone. The molecular mechanisms underlying GC-induced positive GC response element [(+)GRE]-mediated activation of transcription...
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Detection of patterns in sound sequences [Neuroscience]
We use behavioral methods, magnetoencephalography, and functional MRI to investigate how human listeners discover temporal patterns and statistical regularities in complex sound sequences. Sensitivity to patterns is fundamental to sensory processing, in particular in the auditory system, because most auditory signals only have meaning as successions over time. Previous evidence...
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Spectral structure of intrinsic networks [Neuroscience]
Intrinsic covariation of brain activity has been studied across many levels of brain organization. Between visual areas, neuronal activity covaries primarily among portions with similar retinotopic selectivity. We hypothesized that spontaneous interareal coactivation is subserved by neuronal synchronization. We performed simultaneous high-density electrocorticographic recordings across the dorsal aspect of several...
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A slow growth bacterial transcription factor [Microbiology]
Microbial quiescence and slow growth are ubiquitous physiological states, but their study is complicated by low levels of metabolic activity. To address this issue, we used a time-selective proteome-labeling method [bioorthogonal noncanonical amino acid tagging (BONCAT)] to identify proteins synthesized preferentially, but at extremely low rates, under anaerobic survival conditions...
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Subunit arrangement in a GluClR [Physiology]
The invertebrate glutamate-gated chloride-selective receptors (GluClRs) are ion channels serving as targets for ivermectin (IVM), a broad-spectrum anthelmintic drug used to treat human parasitic diseases like river blindness and lymphatic filariasis. The native GluClR is a heteropentamer consisting of α and β subunit types, with yet unknown subunit stoichiometry and...
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Correction for Sohl et al., Probing the structural and molecular basis of nucleotide selectivity by human mitochondrial DNA polymerase {gamma} [Correction]
BIOCHEMISTRY Correction for "Probing the structural and molecular basis of nucleotide selectivity by human mitochondrial DNA polymerase γ," by Christal D. Sohl, Michal R. Szymanski, Andrea C. Mislak, Christie K. Shumate, Sheida Amiralaei, Raymond F. Schinazi, Karen S. Anderson, and Y. Whitney Yin, which appeared in issue 28, July 14,...
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Correction to Supporting Information for Rosenzweig et al., Assessing agricultural risks of climate change in the 21st century in a global gridded crop model intercomparison [SI Correction]
AGRICULTURAL SCIENCES, SUSTAINABILITY SCIENCE Correction to Supporting Information for "Assessing agricultural risks of climate change in the 21st century in a global gridded crop model intercomparison," by Cynthia Rosenzweig, Joshua Elliott, Delphine Deryng, Alex C. Ruane, Christoph Müller, Almut Arneth, Kenneth J. Boote, Christian Folberth, Michael Glotter, Nikolay Khabarov, Kathleen...
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Correction for Ling et al., Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution [Correction]
EVOLUTION Correction for "Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution," by Shaoping Ling, Zheng Hu, Zuyu Yang, Fang Yang, Yawei Li, Pei Lin, Ke Chen, Lili Dong, Lihua Cao, Yong Tao, Lingtong Hao, Qingjian Chen, Qiang Gong, Dafei Wu, Wenjie Li, Wenming...
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Correction for Ogasawara et al., Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition [Correction]
NEUROSCIENCE Correction for "Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition," by Daisuke Ogasawara, Hui Deng, Andreu Viader, Marc P. Baggelaar, Arjen Breman, Hans den Dulk, Adriann M. C. H. van den Nieuwendijk, Marjolein Soethoudt, Tom van der Wel, Juan Zhou, Herman S. Overkleeft,...
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Social regulation of gene expression in zebrafish [Psychological and Cognitive Sciences]
Group living animals must be able to express different behavior profiles depending on their social status. Therefore, the same genotype may translate into different behavioral phenotypes through socially driven differential gene expression. However, how social information is translated into a neurogenomic response and what are the specific cues in a...
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Latent EBV sensing via exosomal small RNA transfer [Microbiology]
Complex interactions between DNA herpesviruses and host factors determine the establishment of a life-long asymptomatic latent infection. The lymphotropic Epstein–Barr virus (EBV) seems to avoid recognition by innate sensors despite massive transcription of immunostimulatory small RNAs (EBV-EBERs). Here we demonstrate that in latently infected B cells, EBER1 transcripts interact with...
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T-cell-intrinsic Tif1{alpha}/Trim24 regulates allergy [Immunology and Inflammation]
There is a paucity of new therapeutic targets to control allergic reactions and forestall the rising trend of allergic diseases. Although a variety of immune cells contribute to allergy, cytokine-secreting αβ+CD4+ T-helper 2 (TH2) cells orchestrate the type-2–driven immune response in a large proportion of atopic asthmatics. To identify previously...
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MINCR is a MYC-induced lncRNA [Biological Sciences]
Based on novel correlation analyses in RNA-seq data from normal tissues and from Burkitt lymphoma (BL) cell lines, Hart et al. (1) suggest that MINCR is not a MYC-induced long noncoding (lnc) RNA. We thank the authors for providing additional analyses, but we do not think these data prove that...
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TCF7L1 in HP axis development [Developmental Biology]
Aberrant embryonic development of the hypothalamus and/or pituitary gland in humans results in congenital hypopituitarism (CH). Transcription factor 7-like 1 (TCF7L1), an important regulator of the WNT/β-catenin signaling pathway, is expressed in the developing forebrain and pituitary gland, but its role during hypothalamo–pituitary (HP) axis formation or involvement in human...
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Structure of NDP-forming Ac-CoA synthetase [Biochemistry]
The NDP-forming acyl-CoA synthetases (ACDs) catalyze the conversion of various CoA thioesters to the corresponding acids, conserving their chemical energy in form of ATP. The ACDs are the major energy-conserving enzymes in sugar and peptide fermentation of hyperthermophilic archaea. They are considered to be primordial enzymes of ATP synthesis in...
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Seafood Consumption, Mercury, and Brain Neuropathology in Older Adults
This cohort study describes correlations and associations between premortem seafood intake, postmortem brain mercury levels, and postmortem Alzheimer disease neuropathology in older adults. Read the article at: http://bit.ly/1nREFJx.
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National Cluster-Randomized Trial of Duty-Hour Flexibility in Surgical Training
In response to concerns about patient safety and resident well-being, the Accreditation Council for Graduate Medical Education (ACGME) introduced national regulations in 2003 that limited resident duty periods to 80 hours per week, capped overnight shift lengths, and mandated minimum time off…
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Establishment of Genome-edited Human Pluripotent Stem Cell Lines: From Targeting to Isolation
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Stem cell-like Xenopus Embryonic Explants to Study Early Neural Developmental Features In Vitro and In Vivo
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Successful diagnosis of intrahepatic splenosis mimicking hepatic tumor
Publication date: Available online 1 February 2016
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Zeng-Lei He, Xiao Xu, Qing-Hong Ke, Shu-Sen Zheng
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Toward Optimum Benefit-Risk and Reduced Access Lag For Cancer Drugs in Asia: A Global Development Framework Guided by Clinical Pharmacology Principles
Delay in approval ('drug lag') of new anticancer therapies in Asia has led to increased interest in simultaneous, global clinical development inclusive of Asia. Anticancer agents often have a narrow therapeutic window, making characterization of pharmacokinetics (PK), pharmacodynamics, and safety crucial for maximizing benefit/risk in Asian populations. Herein, we present a global oncology drug development framework informed by quantitative clinical pharmacology, including an exposure-matched dosing strategy when clinically significant PK differences are encountered in Asia.
This article is protected by copyright. All rights reserved
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Distribution patterns of stone-tool reduction: Establishing frames of reference to approximate occupational features and formation processes in Paleolithic societies
Publication date: March 2016
Source:Journal of Anthropological Archaeology, Volume 41
Author(s): Juan I. Morales
The main goal of this work is to illustrate the interpretative potential of regionally oriented tool-use-life approaches to infer patterns of mobility, occupational intensity, and assemblage formation processes. We apply a wide reduction analysis to 15 Late Upper Paleolithic lithic assemblages. We perform an exploratory data analysis to observe reduction intensity tendencies among the different assemblages, and we characterize reduction distribution patterns using Weibull probability distribution functions. To avoid sampling effects, resampling and bootstrapping were performed. The Weibull profiles of the analyzed data show different degrees of occupational intensity and/or length that are not observable through the classical techno-typological approaches. A referential reduction space is also simulated to create a frame to interpret our results in a more absolute scale.
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La duplication rectale de l’adulte : une cause exceptionnelle de masse pelvienne
Résumé
La duplication rectale est une anomalie constitutionnelle rare du tube digestif, elle représente 5 % des duplications digestives. Son diagnostic se fait habituellement au cours de la période néonatale ou pendant les premières années de vie et ce n'est qu'exceptionnellement que son diagnostic reste méconnu jusqu'à l'âge adulte.
Nous rapportons ici le cas d'une duplication rectale chez une femme de 41 ans se plaignant de douleurs pelviennes. L'examen clinique suivi des examens complémentaires ont suspecté le diagnostic. La patiente est opérée par un abord antérieur isolé, permettant l'exérèse de la totalité de la masse kystique. L'examen anatomopathologique confirme le diagnostic de duplication rectale kystique postérieure non communicante. L'évolution postopératoire est satisfaisante sans morbidité sur un recul de 20 mois.
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Facteurs de risque d’hémorragies digestives par rupture de varices oesophagiennes en République Centrafricaine
Résumé
Objectif
Déterminer les facteurs de risque de rupture des varices oesophagiennes et/ou cardiotubérositaires (VOCT) au cours de cirrhose chez les patients de Bangui, République Centrafricaine (RCA).
Patients et méthodes
Une étude longitudinale descriptive et analytique d'une durée de 13 mois a porté sur tous les patients consentant des deux sexes ayant des VOCT diagnostiquées à l'endoscopie digestive haute.
Résultats
Mille deux cent trente-neuf patients ont eu une endoscopie digestive haute dans « l'hôpital universitaire de l'Amitié » de Bangui (RCA). Parmi ces patients, 156 (12,6 %) avaient des varices oesophagiennes associées dans 11 cas à des varices cardiotubérositaires, 109 hommes (69,9 %) et 47 femmes (30,1 %), sex ratio (H/F) = 2,32. L'âge moyen était de 41 ans (extrêmes 17 à 86 ans). Une hémorragie digestive a révélé les VOCT dans 73 cas (46,8 %), entraînant le décès dans 19 cas. En analyse multivariée, la rupture des VOCT était liée à la présence de signes rouges endoscopiques et à un taux de prothrombine ≤ 50 %.
Conclusion
En RCA, la rupture des VOCT était souvent révélatrice de l'hypertension portale en rapport avec une cirrhose, principalement d'étiologie virale, et était associée aux signes endoscopiques prédictifs et à l'insuffisance hépatocellulaire.
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Dual-Frequency Alternating Current Designer Waveform for Reliable Voltammetric Determination of Electrode Kinetics Approaching the Reversible Limit
Analytical Chemistry
DOI: 10.1021/acs.analchem.5b04354
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Detection of Borrelia burgdorferi sensu lato and spotted fever group rickettsiae in hard ticks (Acari, Ixodidae) parasitizing bats in Poland
Abstract
A total of 491 Ixodes vespertilionis and 8 Ixodes ricinus collected from bats and cave walls in southern Poland between 2010 and 2012 were examined by the polymerase chain reaction for tick-transmitted pathogens. PCR analysis for Borrelia burgdorferi s.l., Rickettsia spp., and Anaplasma phagocytophilum yielded negative results for all I. vespertilionis. DNA of Rickettsia helvetica was detected in three specimens of I. ricinus attached to Rhinolophus hipposideros or Myotis myotis, while Borrelia garinii was found in one tick parasitizing Myotis daubentonii. These pathogens were recorded for the first time in hard ticks that parasitized bats.
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Identification and characterization of Theileria ovis surface protein (ToSp) resembled TaSp in Theileria annulata
Abstract
Ovine theileriosis is an important hemoprotozoal disease of sheep and goats in tropical and subtropical regions which caused high economic loses in the livestock industry. Theileria annulata surface protein (TaSp) was used previously as a tool for serological analysis in livestock. Since the amino acid sequences of TaSp is, at least, in part very conserved in T. annulata, Theileria lestoquardi and Theileria china I and II, it is very important to determine the amino acid sequence of this protein in Theileria ovis as well, to avoid false interpretation of serological data based on this protein in small animal. In the present study, the nucleotide sequence and amino acid sequence of T. ovis surface protein (ToSp) were determined. The comparison of the nucleotide sequence of ToSp showed 96, 96, 99, and 86 % homology to the corresponding nucleotide sequence of TaSp genes by T. annulata, T. China I, T. China II and T. lestoquardi, previously registered in GenBank under accession nos. AJ316260.1, AY274329.1, DQ120058.1, and EF092924.1 respectively. The amino acid sequence analysis showed 95, 81, 98 and 70 % homology to the corresponding amino acid sequence of T. annulata, T chinaI, T china II and T. lestoquardi, registered in GenBank under accession nos. CAC87478.1, AAP36993.1, AAZ30365.1 and AAP36999.11, respectively. Interestingly, in contrast to the C terminus, a significant difference in amino acid sequence in the N teminus of the ToSp protein could be determined compared to the other known corresponding TaSp sequences, which make this region attractive for designing of a suitable tool for serological diagnosis.
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An updated distribution and hosts: trombiculid mites (Acari: Trombidiformes) associated with small mammals in Yunnan Province, southwest China
Abstract
Trombiculid mites (or chigger mites) are a large group of arthropods, and some of these species are vectors of Orientia tsutsugamushi, the causative agent of tsutsugamushi disease (scrub typhus). Yunnan Province is situated in the southwest of China, and its complicated topography, special altitude gradients, and high biodiversity have aroused the interest of many scientists to study the fauna and species diversity of plants and animals. To replenish our former faunal study, this paper listed all the scientific names of trombiculid mites in Yunnan Province, together with their hosts and collection sites (geographical distribution). A total of 120,138 individuals of trombiculid mites were collected from the body surface of 13,760 small mammal hosts (89.06 % of them are rodents) in 29 collection sites (counties) of Yunnan Province from 2001 to 2013. The 120,138 mites were identified as comprising 2 families (Trombiculidae and Leeuwenhoekiidae), 26 genera, and 274 species. The genus Leptotrombidium had the most abundant species (109 species) of 26 genera. Of the six main vectors of scrub typhus in China, five of them were found in Yunnan. Of the 274 chigger mite species, 23 were determined as the newly recorded species (new records), which were found in Yunnan Province for the first time. The identified 274 species of trombiculid mites in the present paper are much more than those from other provinces in China and even largely exceeded the species of trombiculid mites recorded from some other regions and countries in the world. Based on the formula of Chao 1, the total number of chigger mite species in Yunnan was approximately estimated to be 346 species, and about 72 species might have been missed in our sampling process.
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Antenatal immunisation intentions of expectant parents: Relationship to immunisation timeliness during infancy
Source:Vaccine
Author(s): Cameron C. Grant, Mei-Hua Chen, Dinusha K. Bandara, Emma J. Marks, Catherine A. Gilchrist, Sonia Lewycka, Polly E. Atatoa Carr, Elizabeth M. Robinson, Jan E. Pryor, Carlos A. Camargo, Susan M.B. Morton
BackgroundMost women decide about infant immunisation during pregnancy. However, we have limited knowledge of the immunisation intentions of their partners. We aimed to describe what pregnant women and their partners intended for their future child's immunisations, and to identify associations between parental intentions and the subsequent timeliness of infant immunisation.MethodsWe recruited a cohort of pregnant New Zealand (NZ) women expecting to deliver between April 2009 and March 2010. The cohort included 11% of births in NZ during the recruitment period and was generalisable to the national birth cohort.We completed antenatal interviews independently with mothers and partners. We determined immunisation receipt from the National Immunisation Register and defined timely immunisation as receiving all vaccines (scheduled at 6-weeks, 3- and 5-months) within 30 days of their due date. We described independent associations of immunisation intentions with timeliness using adjusted odds ratios (OR) and 95% confidence intervals (CI).ResultsOf 6172 women, 5014 (81%) intended full immunisation, 245 (4%) partial immunisation, 140 (2%) no immunisation and 773 (13%) were undecided. Of 4152 partners, 2942 (71%) intended full immunisation, 208 (5%) partial immunisation, 83 (2%) no immunisation and 921 (22%) were undecided. Agreement between mothers and partners was moderate (Kappa=0.42).Timely immunisation occurred in 70% of infants. Independent of their partner's intentions, infants of pregnant women who decided upon full immunisation were more likely to be immunised on time (OR=7.65, 95% CI: 4.87−12.18). Independent of the future mother's intentions, infants of partners who had decided upon full immunisations were more likely to be immunised on time (OR=3.33, 95% CI: 2.29−4.84).ConclusionsDuring pregnancy, most future parents intend to fully immunise their child; however, more partners than mothers remain undecided about immunisation. Both future mothers' and future fathers' intentions are independently associated with the timeliness of their infant's immunisations.
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Editorial Board/Aims and Scope
Source:Vaccine, Volume 34, Issue 7
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Clinical experience with the meningococcal B vaccine, Bexsero®: Prospects for reducing the burden of meningococcal serogroup B disease
Source:Vaccine, Volume 34, Issue 7
Author(s): Philip S. Watson, David P.J. Turner
Although rare, invasive meningococcal disease remains an important cause of mortality and morbidity in children and young adults. Vaccines have been successfully introduced to help protect against meningococcal disease caused by serogroups A, C, W and Y, but until recently, a vaccine for serogroup B (MenB) was not available. In many industrialised countries, MenB causes the majority of meningococcal disease. Moreover, MenB outbreaks occur unpredictably, particularly in high-risk populations, such as university students. In 2013, Bexsero® became the first broad-coverage vaccine to be licensed for active immunisation against MenB disease. Bexsero is now licensed in more than 35 countries worldwide for varying age groups, including the EU, Australia, Brazil, Canada, Chile, Uruguay and the USA.Clinical recommendations for the use of Bexsero have been published in several countries. Recommendations include use in high-risk groups, outbreak control and routine infant immunisation. Since initial licensure, considerable clinical experience has been gained. In Canada, 43,740 individuals received Bexsero during a vaccination programme in the Saguenay–Lac-Saint-Jean region of Quebec, where local disease incidence was high. In the USA, Bexsero was administered to >15,000 individuals during two college outbreaks prior to licensure, under an Investigational New Drug protocol. In the UK, the Joint Committee on Vaccination and Immunisation has recommended the inclusion of Bexsero in the routine immunisation schedule for infants. Publically funded vaccination programmes have been initiated in Italy, and there has been widespread use of the vaccine outside of publically reimbursed programmes. Overall, >1,000,000 doses of Bexsero have been distributed in 19 countries worldwide since 2013.The emerging clinical experience with Bexsero is consistent with findings from pre-licensure clinical studies, and no new safety concerns have been identified. Additional data on length of protection, potential impact on meningococcal carriage and transmission and strain coverage have also been published and will be reviewed.
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Impact of a publicly funded monovalent rotavirus vaccination program in the Province of Quebec (Canada)
Source:Vaccine, Volume 34, Issue 7
Author(s): Jeannette L. Comeau, Arnaud Gagneur, Caroline Quach
In November 2011, the province of Quebec, Canada implemented a publicly funded rotavirus (RV) vaccination program using the monovalent RV vaccine (RV1). To assess its impact, trends in passive RV laboratory detection and Emergency Department (ED) visits for gastroenteritis (GE) at two pediatric centers were evaluated.MethodsRV tests performed were extracted from the virology laboratory databases and ED visits for GE between July 1, 2006 and June 30, 2013, from the ED databases of The Montreal Children's Hospital (MCH) and Centre Hospitalier Universitaire de Sherbrooke (CHUS). The percent positive RV tests over time and season duration were assessed using 5-week moving averages. We defined season start and end as the first two and the last two consecutive weeks where the percent positive RV tests were ≥10%, respectively.ResultsComparing the pre- and post-vaccination program periods, a decrease in the proportion of positive RV tests was seen: 15.9% vs. 5.1% (p<0.001). Pre-vaccination program, RV seasons started between December and February, peaked in March or April and ended in May. In 2011–2012, the season started in March, peaked in April, and ended in May. In 2012–2013, the season lasted 3 weeks in May. ED visits for GE decreased post-introduction of the RV1 program: from 4.8% to 3.4% in 2011–2012, and 4.2% in 2012–13 (p<0.001). In children <2 years of age, ED GE visits decreased from 7.5% to 4.8% in 2011–2012, and 5.2% in 2012–2013 (p<0.001). Admissions for GE also decreased significantly from 0.41% of all ED visits to 0.14% in 2011–2012 and 0.22% in 2012–2013 (p<0.005).ConclusionImplementation of a publicly funded RV vaccination program had a major impact on the epidemiology of RV infections in Quebec: RV seasons have started later and been of shorter duration, peak positives were fewer, and ED visits for GE decreased.
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Can thermostable vaccines help address cold-chain challenges? Results from stakeholder interviews in six low- and middle-income countries
Source:Vaccine, Volume 34, Issue 7
Author(s): Debra D. Kristensen, Tina Lorenson, Kate Bartholomew, Shirley Villadiego
IntroductionThis study captures the perspectives of stakeholders at multiple levels of the vaccine supply chain regarding their assessment of challenges with storing vaccines within recommended temperature ranges and their perceptions on the benefits of having vaccines with improved stability, including the potential short-term storage and transport of vaccines in a controlled-temperature chain.MethodsSemi-structured interviews were undertaken with 158 immunization stakeholders in six countries. Interviewees included national decision-makers and advisors involved in vaccine purchasing decisions, national Expanded Programme on Immunization managers, and health and logistics personnel at national, subnational, and health facility levels.ResultsChallenges with both heat and freeze-exposure of vaccines were recognized in all countries, with heat-exposure being a greater concern. Conditions leading to freeze-exposure including ice build-up due to poor refrigerator performance and improper icepack conditioning were reported by 53% and 28% of participants, respectively. Respondents were interested in vaccine products with improved heat/freeze-stability characteristics. The majority of those involved in vaccine purchasing indicated they would be willing to pay a US$0.05 premium per dose for a freeze-stable pentavalent vaccine (68%) or a heat-stable rotavirus vaccine (59%), although most (53%) preferred not to pay the premium for a heat-stable pentavalent vaccine if the increased stability required changing from a liquid to a lyophilized product. Most respondents (73%) were also interested in vaccines labeled for short-term use in a controlled-temperature chain. The majority (115/158) recognized the flexibility this would provide during outreach or should cold-chain breaks occur. Respondents were also aware that possible confusion might arise and additional training would be required if handling conditions were changed for some, but not all vaccines.ConclusionParticipating immunization stakeholders recognized the benefits of vaccine products with improved stability characteristics and of labeling vaccines for controlled-temperature chain use as a means to help address cold-chain issues in their immunization programs.
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A trivalent vaccine candidate against hepatitis E virus, norovirus, and astrovirus
Source:Vaccine, Volume 34, Issue 7
Author(s): Ming Xia, Chao Wei, Leyi Wang, Dianjun Cao, Xiang-Jin Meng, Xi Jiang, Ming Tan
Hepatitis E virus (HEV), norovirus (NoV), and astrovirus (AstV) are enterically-transmitted viral pathogens causing epidemic or endemic hepatitis (HEV) and gastroenteritis (NoV and AstV) respectively in humans, leading to significant morbidity and mortality worldwide. While a recombinant subunit vaccine against HEVs is available in China, there is no commercial vaccine or antiviral against NoV or AstV. We report here our development of a trivalent vaccine against the three viral pathogens through our new polymer vaccine technology. All HEV, NoV, and AstV are non-enveloped RNA viruses covered by a protein capsid, featuring surface protruding (P) proteins that are responsible for virus–host interaction. These dimeric P proteins elicit neutralizing antibody and are good targets for subunit vaccine development. The trivalent subunit vaccine was developed by fusion of the dimeric P domains of the three viruses together that formed tetramers. This trivalent vaccine elicited significantly higher antibody responses in mice against all three P domains than those induced by a mixture of the three free P domains (mixed vaccine). Furthermore, the post-immune antisera of the trivalent vaccine showed significantly higher neutralizing titers against HEV infection in cell culture and higher blocking activity against NoV binding to HBGA ligands than those of the post-immune sera of the mixed vaccine. Thus, the trivalent vaccine is a promising vaccine candidate against HEV, NoV, and AstV.
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Intradermal vaccination with un-adjuvanted sub-unit vaccines triggers skin innate immunity and confers protective respiratory immunity in domestic swine
Source:Vaccine, Volume 34, Issue 7
Author(s): Jean-Benoît Le Luduec, Sabine Debeer, Fabienne Piras, Christine Andréoni, Florence Boudet, Philippe Laurent, Dominique Kaiserlian, Bertrand Dubois
Intradermal (ID) vaccination constitutes a promising approach to induce anti-infectious immunity. This route of immunization has mostly been studied with influenza split-virion vaccines. However, the efficacy of ID vaccination for sub-unit vaccines in relation to underlying skin innate immunity remains to be explored for wider application in humans. Relevant animal models that more closely mimic human skin immunity than the widely used mouse models are therefore necessary. Here, we show in domestic swine, which shares striking anatomic and functional properties with human skin, that a single ID delivery of pseudorabies virus (PRV) glycoproteins without added adjuvant is sufficient to trigger adaptive cellular and humoral immune responses, and to confer protection from a lethal respiratory infection with PRV. Analysis of early events at the skin injection site revealed up-regulation of pro-inflammatory cytokine and chemokine genes, recruitment of neutrophils and monocytes and accumulation of inflammatory DC. We further show that the sustained induction of pro-inflammatory cytokine genes results from the combined effects of skin puncture, liquid injection in the dermis and viral antigens. These data highlight that immune protection against respiratory infection can be induced by ID vaccination with a subunit vaccine and reveal that adjuvant requirements are circumvented by the mechanical and antigenic stress caused by ID injection, which triggers innate immunity and mobilization of inflammatory DC at the immunization site. ID vaccination with sub-unit vaccines may thus represent a safe and efficient solution for protection against respiratory infections in swine and possibly also in humans, given the similarity of skin structure and function in both species.
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Adverse events following immunization in patients with primary immunodeficiencies
Source:Vaccine
Author(s): Juan David Sarmiento, Fabio Villada, Julio Cesar Orrego, Jose Luis Franco, Claudia M. Trujillo-Vargas
BackgroundAdverse events following immunization (AEFI) requires special consideration in patients with primary immunodeficiency diseases (PID) because they may represent a "red flag" for the initial diagnosis and may cause disease complications. Therefore, the definition of appropriate vaccination schemes is a major issue in PID. The aim of this study is to describe the AEFI in a cohort of PID patients.MethodsMedical records from 379 PID patients were included. AEFI severity was classified according to the WHO 1999 guidelines. Causality was assessed using the Clinical Immunization Safety Assessment (CISA) 2009 criteria.ResultsEvidence of AEFI was found in 26 medical records and represented a total of 29 reactions. Most of the AEFI were observed in patients with idiopathic hypogammaglobulinemia (IHG), chronic granulomatous disease (CGD) and severe combined immunodeficiency (SCID), representing 10, 4 and 4 cases, respectively. A total of 21 reactions were associated with replicative vaccines, 7 of which were serious cases related to Bacille Calmette-Guérin (BCG). BCG was also the vaccine more often associated with definitive AEFI in PID. In addition to BCG-related complications, seizures were the most serious AEFI among PID patients.ConclusionsOur study included a large cohort of PID patients and confirmed an increased risk of serious AEFI in these populations. The design and implementation of neonatal screening strategies for the early detection of congenital lymphopenias and other PID are urgently needed to avoid serious complications of the BCG vaccine usually applied immediately after birth. Our findings also support the use of the acellular pertussis vaccine to minimize the appearance of seizures in PID patients vaccinated with diphtheria, pertussis and tetanus (DPT).
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Infant vaccination timing: Beyond traditional coverage metrics for maximizing impact of vaccine programs, an example from southern Nepal
Publication date: 10 February 2016
Source:Vaccine, Volume 34, Issue 7
Author(s): Michelle M. Hughes, Joanne Katz, Janet A. Englund, Subarna K. Khatry, Laxman Shrestha, Steven C. LeClerq, Mark Steinhoff, James M. Tielsch
BackgroundImmunization programs currently measure coverage by assessing the proportion of children 12–24 months who have been immunized but this does not address the important question of when the scheduled vaccines were administered. Data capturing the timing of vaccination in first 6 months, when severe disease is most likely to occur, are limited.ObjectiveTo estimate the time to Bacillus Calmette–Guérin (BCG) (recommended at birth), diphtheria-tetanus-pertussis-H, influenza b-hepatitis B (DTP-Hib-HepB), and oral polio vaccine (OPV) (recommended at 6, 10, and 14 weeks) vaccinations and risk factors for vaccination delay in infants <6 months of age in a district in southern Nepal where traditional coverage metrics are high.Design/methodsInfants enrolled in a randomized controlled trial of maternal influenza vaccination were visited weekly at home from birth through age 6 months to ascertain if any vaccinations had been given in the prior week. Infant, maternal, and household characteristics were recorded. BCG, DTP-Hib-HepB, and OPV vaccination coverage at 4 and 6 months was estimated. Time to vaccination was estimated through Kaplan–Meier curves; Cox-proportional hazards models were used to examine risk factors for delay for the first vaccine.ResultsThe median age of BCG, first OPV and DTP-Hib-HepB receipt was 22, 21, and 18 weeks, respectively. Almost half of infants received no BCG by age 6 months. Only 8% and 7% of infants had received three doses of OPV and DTP-Hib-HepB, respectively, by age 6 months.ConclusionA significant delay in receipt of infant vaccines was found in a prospective, population-based, cohort in southern Nepal despite traditional coverage metrics being high. Immunization programs should consider measuring time to receipt relative to the official schedule in order to maximize benefits for disease control and child health.
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Evaluation of the non-toxic mutant of the diphtheria toxin K51E/E148K as carrier protein for meningococcal vaccines
Source:Vaccine
Author(s): S. Pecetta, B. Vijayakrishnan, M.R. Romano, D. Proietti, P. Lo Surdo, C. Balocchi, E. Mori, B.G. Davis, F. Berti
Diphtheria toxin mutant CRM197 is a common carrier protein for glycoconjugate vaccines, which has been proven an effective protein vector for, among others, meningococcal carbohydrates. The wide-range use of this protein in massive vaccine production requires constant increase of production yields and adaptability to an ever-growing market. Here we compare CRM197 with the alternative diphtheria non-toxic variant DT-K51E/E148K, an inactive mutant that can be produced in the periplasm of Escherichia coli. Biophysical characterization of DT-K51E/E148K suggested high similarity with CRM197, with main differences in their alpha-helical content, and a suitable purity for conjugation and vaccine preparation. Meningococcal serogroup A (MenA) glycoconjugates were synthesized using CRM197 and DT-K51E/E148K as carrier proteins, obtaining the same conjugation yields and comparable biophysical profiles. Mice were then immunized with these CRM197 and DT-K51E/E148K conjugates, and essentially identical immunogenic and protective effects were observed. Overall, our data indicate that DT-K51E/E148K is a readily produced protein that now allows the added flexibility of E. coli production in vaccine development and that can be effectively used as protein carrier for a meningococcal conjugate vaccine.
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Immunogenicity and efficacy of alphavirus-derived replicon vaccines for respiratory syncytial virus and human metapneumovirus in nonhuman primates
Source:Vaccine, Volume 34, Issue 7
Author(s): John T. Bates, Jennifer A. Pickens, Jennifer E. Schuster, Monika Johnson, Sharon J. Tollefson, John V. Williams, Nancy L. Davis, Robert E. Johnston, Nancy Schultz-Darken, James C. Slaughter, Frances Smith-House, James E. Crowe
Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are major causes of illness among children, the elderly, and the immunocompromised. No vaccine has been licensed for protection against either of these viruses. We tested the ability of two Venezuelan equine encephalitis virus-based viral replicon particle (VEE-VRP) vaccines that express the hRSV or hMPV fusion (F) protein to confer protection against hRSV or hMPV in African green monkeys. Animals immunized with VEE-VRP vaccines developed RSV or MPV F-specific antibodies and serum neutralizing activity. Compared to control animals, immunized animals were better able to control viral load in the respiratory mucosa following challenge and had lower levels of viral genome in nasopharyngeal and bronchoalveolar lavage fluids. The high level of immunogenicity and protective efficacy induced by these vaccine candidates in nonhuman primates suggest that they hold promise for further development.
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The Use of Aspiration Catheter Systems for Embolic Protection during Intracranial Vertebral Artery Angioplasty and Stenting
Background: Posterior circulation strokes comprise approximately 20-25% of all strokes of ischemic origin. Strokes affecting this area carry a significantly higher risk for subsequent stroke or death as compared to anterior circulation strokes. Embolic protection device (EPD) use for carotid artery stenosis has translated into percutaneous interventions of proximal vertebral artery (VA) stenosis. However, the use of EPDs when treating intracranial lesions has yet to be studied and may not be feasible as the vessel caliber is frequently smaller than in existing devices. Objective: The aim of this study is to describe a proximal aspiration technique used during the treatment of intracranial VA and basilar artery (BA) atherosclerotic disease. Methods: Proximal embolic protection was utilized during the treatment of intracranial VA/BA stenosis with angioplasty and stenting in patients with medically refractory disease. Results: Three patients with severe symptomatic posterior circulation stenosis refractory to medical management were treated with angioplasty and stenting utilizing proximal aspiration. Pre- and post-treatment angiograms and MRIs were compared. Treated vascular stenoses were significantly improved, without new neurological deficits or ischemic injury identified on imaging. Conclusions: The proposed technique of proximal embolic protection may help overcome the challenge of embolus propagation inherent to the treatment modality that was encountered during the treatment of intracranial VA/BA stenosis.
Intervent Neurol 2015;4:113-119
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Recombinant Brain Natriuretic Peptide for the Prevention of Contrast-Induced Nephropathy in Patients with Chronic Kidney Disease Undergoing Nonemergent Percutaneous Coronary Intervention or Coronary Angiography: A Randomized Controlled Trial
The role of brain natriuretic peptide (BNP) in the prevention of contrast-induced nephropathy (CIN) is unknown. This study aimed to investigate BNP's effect on CIN in chronic kidney disease (CKD) patients undergoing elective percutaneous coronary intervention (PCI) or coronary angiography (CAG). The patients were randomized to BNP (0.005 μg/kg/min before contrast media (CM) exposure and saline hydration, ) or saline hydration alone (). Cystatin C, serum creatinine (SCr) levels, and estimated glomerular filtration rates (eGFR) were assessed at several time points. The primary endpoint was CIN incidence; secondary endpoint included changes in cystatin C, SCr, and eGFR. CIN incidence was significantly lower in the BNP group compared to controls (6.6% versus 16.5%, ). In addition, a more significant deterioration of eGFR, cystatin C, and SCr from 48 h to 1 week () was observed in controls compared to the BNP group. Although eGFR gradually deteriorated in both groups, a faster recovery was achieved in the BNP group. Multivariate logistic regression revealed that using >100 mL of CM (odds ratio: 4.36, ) and BNP administration (odds ratio: 0.21, ) were independently associated with CIN. Combined with hydration, exogenous BNP administration before CM effectively decreases CIN incidence in CKD patients.
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Development of a Murine Infection Model with Leishmania killicki, Responsible for Cutaneous Leishmaniosis in Algeria: Application in Pharmacology
In Algeria, Leishmania infantum, Leishmania major, and Leishmania killicki (Leishmania tropica) are responsible for cutaneous leishmaniosis. We established a murine model of L. killicki infection to investigate its infective capacity, some immunophysiopathological aspects, and its suitability for pharmacological purposes. Following the injection of L. major or L. killicki metacyclic promastigotes in the ear dermis of BALB/c mice, the course of infection was followed. The infection with L. killicki caused slower lesion formation than with L. major. The presence of L. killicki or L. major DNA and parasites was detected in the ear dermis and in lymph nodes, spleen, and liver. Lesions induced by L. killicki were nonulcerative in their aspect, whereas those caused by L. major were highly ulcerative and necrotic, which matches well with the lesion phenotype reported in humans for L. killicki and L. major, respectively. The treatment of L. killicki lesions by injection of Glucantime® significantly reduced the lesion thickness and parasite burden. Ear dermal injection of BALB/c mice constitutes a model to study lesions physiopathology caused by L. killicki and presents interest for in vivo screening of new compounds against this pathogen, emerging in Algeria.
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The Synthesis and Evaluations of the 68Ga-Lissamine Rhodamine B (LRB) as a New Radiotracer for Imaging Tumors by Positron Emission Tomography
Purpose. The aim of this study is to synthesize and evaluate 68Ga-labeled Lissamine Rhodamine B (LRB) as a new radiotracer for imaging MDA-MB-231 and MCF-7 cells induced tumor mice by positron emission tomography (PET). Methods. Firstly, we performed the radio synthesis and microPET imaging of 68Ga(DOTA-LRB) in athymic nude mice bearing MDA-MB-231 and MCF-7 human breast cancer xenografts. Additionally, the evaluations of 18F-fluorodeoxyglucose (FDG), as a glucose metabolism radiotracer for imaging tumors in the same xenografts, have been conducted as a comparison. Results. The radiochemical purity of 68Ga(DOTA-LRB) was >95%. MicroPET dynamic imaging revealed that the uptake of 68Ga(DOTA-LRB) was mainly in normal organs, such as kidney, heart, liver, and brain and mainly excreted from kidney. The MDA-MB-231 and MCF-7 tumors were not clearly visible in PET images at 5, 15, 30, 40, 50, and 60 min after injection of 68Ga(DOTA-LRB). The tumor uptake values of 18F-FDG were and %ID/g in MDA-MB-231 and MCF-7 tumor xenografts, respectively. Conclusions. 68Ga(DOTA-LRB) can be easily synthesized with high radiochemical purity and stability; however, it may be not an ideal PET radiotracer for imaging of MDR-positive tumors.
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Evaluation of Hepatotoxicity with Treatment Doses of Flucytosine and Amphotericin B for Invasive Fungal Infections
Invasive fungal infection is a well-known cause of morbidity and mortality in immunocompromised patients. In this study we aimed to evaluate the hepatotoxicity induced by combined therapy of flucytosine and amphotericin B, at three different doses administered to mice for 14 days: 50 mg/kg flucytosine and 300 μg/kg amphotericin B; 100 mg/kg flucytosine and 600 μg/kg amphotericin B; 150 mg/kg flucytosine and 900 μg/kg amphotericin B. Liver injuries were evaluated by analysis of optic and electron microscopy samples, changes in TNF-α, IL-6, and NF-κB inflammation markers levels of expression, and evaluation of mRNA profiles. Histological and ultrastructural analysis revealed an increase in parenchymal and portal inflammation in mice and Kupffer cells activation. Combined antifungal treatment stimulated activation of an inflammatory pathway, demonstrated by a significant dose-dependent increase of TNF-α and IL-6 immunoreactivity, together with mRNA upregulation. Also, NF-κB was activated, as suggested by the high levels found in hepatic tissue and upregulation of target genes. Our results suggest that antifungal combined therapy exerts a synergistic inflammatory activation in a dose-dependent manner, through NF-κB pathway, which promotes an inflammatory cascade during inflammation. The use of combined antifungal therapy needs to be dose limiting due to the associated risk of liver injury, especially for those patients with hepatic dysfunction.
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Clinical Effect and Mechanism of Yisui Shengxue Granules in Thalassemia Patients with Mild, Moderate, or Severe Anemia
Yisui Shengxue granules, which is a Chinese traditional medicine, can increase hemoglobin, red blood cells, and Ret of thalassemia patients with mild, moderate, and severe anemia and thus relieve clinical anemia symptoms. Studies on mechanism found that Yisui Shengxue granules can increase the proliferation ability of hematopoietic stem cells. Emodin promoted colony forming of hematopoietic stem cells. Yisui Shengxue granules can increase the activity of GSH-PX in bone marrow blood and decreased the severity of inclusion bodies on the cytomembrane of RBCs. YSSXG attenuated anemia symptoms in patients with thalassemia mostly by increasing the proliferation of hematopoietic stem cells and decreasing the hemolysis of RBCs.
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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